Abstract
Advanced Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a poor prognosis. The anti-malaria compounds dihydroartemisinin (DHA) have shown to regulate multiple targets and signaling pathways in cancers, but a global view of its mechanism of action remains elusive. In present study, we integrated network pharmacology and in vitro and in vivo experimental models to investigate the mechanisms of DHA in preventing NSCLC proliferation. We first proved that DHA inhibits the growth of lung cancer via inducing cell apoptosis and cell cycle arrest, then we integrated information from publicly available databases to predict interactions between DHA and its potential targets in NSCLC, as well as the signaling pathways involved. In this way we identified 118 common targets of DHA and NSCLC, and further analyzed with the correlation between these targets by KEGG and GO analysis. Our data indicate that mTOR/HIF-1α signaling is one of potential critical pathways involved in DHA-induced tumor inhibition in NSCLC. Finally, the data from human and mouse lung cancer cell lines and in mouse Lewis lung cancer models showed that DHA does decrease the expression level of mTOR and HIF-1α which supported the potential roles of mTOR/HIF-1α Signaling in NSCLC and deserves further investigation.